Cortical glutamatergic and GABAergic inputs support learning-driven hippocampal stability Science

Using dual-color optogenetics combined with intracellular somatic and dendritic recordings, we mapped the functional connectivity from LECGLU and LECGABA inputs to CA3. LECGLU drove excitation in CA3 PNs but also substantial feedforward inhibition that prevented somatic and dendritic spikes. LECGABA exclusively inhibited a subset of soma-targeting local CA3 inhibitory neurons recruited by LECGLU, thereby reducing feedforward inhibition onto CA3 PNs. This LECGABA-mediated disinhibition selectively increased CA3 PN somatic, but not dendritic, spiking in response to integrated LECGLU and CA3 feedback but not DG feedforward inputs. Using dual-chemogenetic silencing of CA3-projecting LECGLU or LECGABA and two-photon calcium imaging of CA3 PN somas and dendrites, we tested how this circuit supports memory-related ensemble activity and behavior.